At Press Time

New Criteria for Glaucoma Therapeutics?

NEI/FDA endpoints symposium seeks more clarity.

■ An NEI- and FDA-sponsored conference to be held Sept. 24 at the NEI's Natcher Center in Bethesda, Md., will seek to develop definitions and standards for describing structural changes in the glaucomatous optic nerve and functional changes in vision. These criteria could then be used to set endpoints for clinical trials of new glaucoma therapeutics.

In announcing the conference, an ARVO news release contends that “while functional measures of the presence and progression of glaucomatous optic neuropathy have been developed and are currently in use, they are imprecise and poorly resolved. Likewise, the precision, resolution and rate of change for structural parameters of the optic nerve head and retinal nerve fiber layer are also not yet well-articulated.”

The meeting, part of an NEI/FDA series of Endpoints Symposia, will examine non-IOP glaucoma endpoints. Participants will explore how to in crease the precision of functional measures as well as better articulate the precision, resolution and rate of change for structural parameters of the optic nerve head and retinal nerve fiber layer. In addition, they will examine how best to compare and contrast such structural measures with functional outcomes in patients' vision.

Participants will also look at whether such functional and structural measures can be combined into new endpoints for glaucoma clinical trials to shorten the timeline for clinical trials/development of potential new therapies.

Faculty will include authorities in glaucoma and glaucoma diagnosis, including the newest structural and functional testing instruments and algorithms. FDA representatives will review current optic nerve endpoints used in glaucoma drug and device trials, while researchers will discuss in detail specific techniques and criteria as well as the relationships between structural events and functional outcomes.

Clinical researchers, glaucoma specialists, biotech companies and representatives of glaucoma-related associations are urged to attend this conference.

Interestingly, the announcement of the conference comes just months after a new consensus paper was drafted at the World Glaucoma Association (WGA) meeting. The paper, scheduled to be published later this year, will for the first time assert that a primary consideration in treating and managing glaucoma should be based on what is termed “rate of change.” Key wording in the consensus paper is expected to state that treatment is indicated “when the risks of progressive disease outweigh the risks and potential side effects of treatment.” The new guideline could represent a major boost for the use of advanced instruments such as spectral-domain OCT that use guided progression analysis software to analyze disease progression.

In addition, the WGA is expected to take the position that ophthalmologists who treat glaucoma should take into account structural change as well as functional change in assessing disease progression.

The Appeal of “Key Man” Insurance

A low-priced policy can save a practice.

By Jerry Helzner, Senior Editor

■ In the past few years, two highly respected ophthalmologists in the prime of their lives died tragically one in a parachuting accident and another in the crash of a private plane. Other ophthalmologists have been forced to stop practicing, either temporarily or permanently, because of illness or disability.

The sudden loss of a productive practitioner can cripple or even spell the end of a practice. This is especially true of smaller practices, which tend to have only two or three physicians. However, a practice that buys reasonably priced term life insurance policies on its key practitioners stands a good chance to survive even the death of a partner or principal.

“If it's a solo practice and the doctor dies, it's probably the end of that practice,” says Mark Kropiewnicki, Esq., LLM, CEO of the Health Care Group, Inc., in Plymouth Meeting, Pa. “However, say you have a two-physician practice and one dies suddenly, you still have all the expenses and overhead of a two-physician practice. The insurance payment can buy some time and give the practice a fighting chance to bring in another physician and get that doctor up to speed.”

Mr. Kropiewnicki says the simplest and most cost-effective way to get so-called “key man” (or key employee) insurance protection is to buy a 20-year term whole-life policy with a payout in the neighborhood of $300,000.

Premiums on these policies are not tax-deductible and will vary based on the age and health of the person being insured, but Mr. Kropiewnicki says they can be purchased for as little as $1,000 a year.

“Key man insurance can be very important in maintaining cash flow and providing financial resources to replace a physician,” says James Dawes, chief administrative officer for the Center for Sight in Sarasota, Fla. “However, if a group has significant physician capacity with other quality providers who can take over the physician's practice, the need for such insurance is greatly diminished. I would also recommend that if a group chooses to purchase key man insurance, that a written agreement is put in place with the group ownership as to how the proceeds of an insurance payment are to be used.”

“Some financial planners will try to tie key man insurance in with investments and estate planning but I don't advocate that,” Mr. Kropiewnicki says. “In this instance, the simple, term whole-life policy is the best way to go.”

To protect against a physician's disability, practices can purchase pricier disability insurance or another type of policy called “overhead insurance” that provides payments to keep a practice going during the extended absence of a doctor.

DSEK Graft Thickness and Visual Acuity

Three thicknesses produce similar results.

■ Researchers from the Duke Eye Center set out to assess a relationship between preoperative donor cornea graft thickness and visual acuity outcomes six months after Descemets Stripping Endothelial Keratoplasty (DSEK).

The retrospective review encompassed 209 patients who underwent DSEK and were assessed six months postoperatively at Duke Eye Center. BSCVA was obtained preoperatively and six months postoperatively and was subsequently converted into LogMAR visual acuity for analysis.

Preoperative donor cornea graft thickness was measured via pachymetry during graft preparation. Visual outcomes were compared using graft thickness as a continuous variable. Visual outcomes were also compared between three groups: grafts 100 μm or less (n=29), grafts between 101 and 150 μm (n=137), and grafts 151 μm or greater (n=43). The Kruskal-Wallis test of difference in medians was used to determine significance.

In results presented at the 2010 ARVO meeting, the median visual change for grafts 100 μm or less was −0.204 LogMAR. The median visual change for grafts between 101 and 150 μm was also −0.204 LogMAR. The median visual change for grafts 151 μm or greater was −0.222 LogMAR. The difference in acuity between preoperative vision and vision at the six month time point was not significantly different among the three thickness categories.

The researchers concluded that analysis of visual outcomes six months following DSEK show no statistically significant difference based upon pre-operative graft thickness. Based upon the current analysis, current donor cornea graft preparation protocols do not need amending to favor a certain thickness. Additional analysis of visual outcomes at the one-year or two-year time points in this population is ongoing to determine if significant differences between thickness groups exist later in the course of graft maturity.

Research Digest

New & Noteworthy Journal Articles

Compiled by Andrew E. Mathis, PhD, Medical Editor

► Before you go to the beach… If you prescribe medications that cause photosensitivity as a side effect, then you're already advising your patients to use sunscreen, but it may be even more important to recommend extra eye protection. Reporting their data in the August 2010 issue of Archives of Ophthalmology, a team of ophthalmologists from the University of Wisconsin-Madison state that the use of sun-sensitizing medications increases the risk of cortical cataract.

Taking patients from the Beaver Dam Eye Study, the study authors identified 2,998 people with cortical cataract who were followed over a 15-year period. While no effects were observed of sun-sensitizing medications on the incidence of age-related cataract when controlling for age or sex, when statistical analysis was done on the combination of sun exposure and photosensitivity-causing medications, a statistically significant relationship was seen. Interestingly, no association was found between the use of sunglasses or hats during sun exposure, although there was not a sufficiently large sample size of people using this type of sun protection to draw any firm conclusions.

The study authors suggest that further research on the association between drug photosensitivity, sunlight exposure, and cortical cataract be conducted to take into account variables such as dosages of medications and varying types of ultraviolet light.

► Amblyopia outcomes. Occlusion therapy for pediatric amblyopia has been a standard of care for over a hundred years. Nevertheless, there does not yet exist a universal protocol for the treatment, and results vary. Seeking to fill in this gap in knowledge, scientists from Leicester, UK, and Barbados have collaborated on a retrospective analysis of hospital-based occlusion therapy for amblyopia; their results appear in the August 2010 issue of the British Journal of Ophthalmology.

The authors analyzed treatment notes from 322 children treated between 1996 and 2008 at the Leicester Royal Infirmary; this number was chosen to provide a statistically robust sample size. All patients presented at eight years old or younger. Data analyzed included visual acuity before occlusion, after occlusion and at discharge, duration of occlusion therapy and number of glasses prescribed.

The results were less than rosy: Although patients were treated with long durations of occlusion therapy, on average, visual outcome was unsatisfactory (measured at <6/9 in almost one-third of patients with mixed amblyopia) and unpredictable. However, as another of the variables included in the analysis was compliance, and this was seen to have an association with treatment outcomes, the authors urge better parent education and motivational interventions.

► Contact lens for IOP? The August 2010 issue of the Journal of Glaucoma includes the results of a small study of a new contact lens-embedded sensor to measure IOP. Doctors at the Ohio State University studied the novel device, which was developed by Ziemer Ophthalmic Systems AG (Port, Switzerland), in 12 eyes of 12 patients in sitting and supine positions, and the new sensor was compared to measurements taken with slit lamp-mounted and hand-held sensors. IOP and ocular pulse amplitude (OPA) were taken in all cases.

Supine IOP and OPA measurements were higher using the lens-mounted device than measurements taken in the seated position, but less than the measurements taken with the hand-held device. The lens-mounted sensor had the least variability in measurement, particularly when compared to the hand-held sensor, and statistically calculated limits of agreement were smallest when comparing the new sensor with the slit-lamp-mounted sensor, indicating very good agreement between the measurements.

While the results here are promising, the study authors point out a few shortcomings with the new sensor as currently configured. Most importantly, the current shape of the lens-mounted sensor does not allow for anatomical variability, and three initial enrollees in the trial had to be disqualified because they could not be fitted with the lens. Also, the device is not yet wireless, so the need to be connected by wire to machinery limits the device's usefulness currently. Nevertheless, the device brings doctors one step closer to being able to continuously monitor IOP

► Singling out double vision. A short review article in the September 2010 issue of Current Opinions in Ophthalmology examines diplopia rates following combined phacoemulsification and LASIK procedures. Ophthalmologists from the Wills Eye Institute and Thomas Jefferson University, both in Philadelphia, report a diplopia rate of between 0.23% and 0.98% in phaco patients given retrobulbar anesthesia who had ocular misalignment following their surgeries; this rate is nearly eliminated, however, when topical anesthesia is used instead.

Causes of diplopia following combined procedures include new-onset accommodative amblyopia, systemic disease and preoperative strabismus, with the latter of these accounting for the largest percentage when topical anesthesia is used over retrobulbar anesthesia.

These findings underscore the importance of preoperative screening for strabismus, as well as the use of topical anesthesia. Family history is an important part of this screening process, as cases of strabismus that are not detectable with the naked eye can still be problematic, and a high percentage of patients with strabismus have an immediately family member with the disorder.

Retina Roundup

Timely and Important Retina News of Interest to All Ophthalmologists

Compiled by Andrew E. Mathis, PhD, Medical Editor

► Avastin for RVO. Ranibizumab recently received FDA approval for use in retinal vein occlusion, so it is not surprising that studies have undertaken testing parent drug bevacizumab for the same condition. The results of a small trial appear in the August 2010 British Journal of Ophthalmology. The study, conducted in Spain, examined 46 eyes with central or branch RVO treated with bevacizumab over a six-month period. Mean number of injections given to patients was 3.7 for branch RVO patients and 4.6 for the central RVO group. Six-month mean change in visual acuity was an improvement of 0.44 and was statistically significant, as was the mean 268.2-μm drop in macular thickness.

The authors conclude that bevacizu mab can be an effective primary treatment for RVO, although such treatment requires several injections, thus increasing the risk of certain side effects. As the retinal community awaits results of the head-to-head comparison of bevacizumab to ranibizu mab in the CATT trial, it is likely such trials will continue.

► ROP compensation. There is no uniform standard in the US for physician reimbursements for treating retinopathy of prematurity, according to an article in the August 2010 issue of Archives of Ophthalmology, nor is there any standard for malpractice insurance coverage.

The authors of the article, from the medical school at the University of Colorado Denver, found that income generation for performing ROP screening was only half of what the typical pediatric ophthalmologist would earn if he or she instead performed surgery or saw patients in a clinic rather than neonatal centers, which tend to incur more regular travel costs to the doctors.

An unexpected finding was that earnings were best for respondents from the southern United States, where, conversely incomes have traditionally been lower across industries. However, as the study was small (12 respondents), how reliable the data are remains to be seen.

► Snellen vs. ETDRS. A study published in the July-August 2010 issue of Retina may have importance for ophthalmologists beyond retina subspecialists, as the authors of the article argue for conversion of Snellen visual acuity measurements to the measurements established for the Early Treatment of Diabetic Retinopathy Study (ETDRS).

The rationale for the conversion, according to the authors, from the University of Miami's Bascom Palmer Eye Institute, is greater ease of statistical manipulation with the ETDRS data. Using an approximated ETDRS score, they argue — rather than a logMAR score, as is now often the case — would decrease the number of computations of statistically significant results that turn out later not to be borne out. Until more rigorous study is carried out, the authors urge caution in labeling results as approximations.

► Macugen as maintenance therapy. Wet AMD patients who begin therapy with ranibizumab or bevacizumab can successfully switch to Macugen for maintenance therapy after the induction phase, according to a recent study in The British Journal of Ophthalmology. In the open-label LEVEL study of 568 patients, mean visual acuity improved by 15.9 letters (from 49.6 letters to 65.5 letters) during the induction phase and remained relatively stable at 61.8 letters at the end of a 54-week Macugen maintenance phase.